We are a small step closer to the day when two women or two men could have biological children of their own, thanks to improved methods for creating mice with same-sex parents. But the work also shows that there is an enormous amount still to do before this could be attempted in humans.
“It is never too much to emphasise the risks, and the importance of safety, before any human experiment is involved,” says Wei Li at the Chinese Academy of Sciences in Beijing. “But we think our work does take it closer.”
The greatest obstacle to creating babies from parents of the same sex is a phenomenon called imprinting. In mammals, certain genes are switched off in the sperm genome, by adding epigenetic markers to the DNA. These markers don’t change the underlying DNA sequence, but they ensure the gene is not expressed. Different genes are turned off in eggs.
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Battle between the sexes
This is the result of a battle between the sexes, with males trying to boost the growth of their offspring at the expense of females, and females fighting back. Imprinting means that if you somehow combine the genomes of two females, or two males, in an egg and kickstart development, the resulting embryo will die.
But in 2004 a team in Japan managed to create the mouse – the first ever mammal with two mothers. They achieved this deleting a piece of DNA in one of the genomes to mimic the effect of imprinting – but 500 attempts produced just two mice that survived to adulthood.
Li’s team have greatly improved the success rate by deleting three bits of DNA to better mimic normal imprinting. They made 200 attempts at creating a mouse with two mothers, succeeding 27 times.  These mice grew normally, whereas those with fewer deletions were abnormally small.
What’s more, Li’s team also created 12 mice with two fathers from 500 attempts, by deleting seven pieces of DNA. However, none survived to adulthood.
This is not the first claim of mice with two fathers. A used a genetic trick to make cells from male mice develop inside females. Females with ovaries derived from the male cells were then mated with normal males. Arguably, this is cheating, and it could not be done in humans.
Li’s mice reveal more about which imprinted genes are crucial for normal development. However, it’s not clear if the results apply to other mammals such as humans – the team will test this by trying to create monkeys with two mothers.
And before we could even think of trying to create babies with same-sex parents, we’d need a way of mimicking imprints without resorting to genetic modification. Not least because the deletions would have harmful effects in later generations.
That might just be possible. Several groups are modifying CRISPR gene-editing tools to add or remove epigenetic markers without changing the underlying DNA sequence.
Li’s team is already testing this approach. “We are trying but we don’t know the answer yet,” he says.
Even if it works, huge safety questions remain. “Faulty imprints do give rise to human diseases,” says Azim Surani of Cambridge University, who discovered the imprinting phenomenon in 1984. Any manipulation of imprints could therefore have serious consequences, he warns.
There are at least 150 key imprinted genes in mammals and some affect things like behaviour as well as growth, points out Surani. So even though the mice with two mothers created by deleting just three bits of DNA appeared healthy, they might have more subtle problems.
Cell Stem Cell
